Steegen Kim, Carmona Sergio, Bronze Michelle, Papathanasopoulos Maria A, van Zyl Gert, Goedhals Dominique, MacLeod William, Sanne Ian, Stevens Wendy S
Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.
National Health Laboratory Services, Johannesburg, South Africa.
PLoS One. 2016 Dec 1;11(12):e0166305. doi: 10.1371/journal.pone.0166305. eCollection 2016.
In order to assess the level of transmitted and/or pre-treatment antiretroviral drug resistance to HIV-1, the World Health Organization (WHO) recommends that regular surveys are conducted. This study's objective was to assess the frequency of HIV-1 antiretroviral drug resistance in patients initiating antiretroviral treatment (ART) in the public sector throughout South Africa.
A prospective cross-sectional survey was conducted using probability proportional to size sampling. This method ensured that samples from each province were proportionally collected, based on the number of patients receiving ART in each region. Samples were collected between March 2013 and October 2014. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to the Stanford Calibrated Population Resistance tool v6.0.
A total of 277 sequences were available for analysis. Most participants were female (58.8%) and the median age was 34 years (IQR: 29-42). The median baseline CD4-count was 149 cells/mm3 (IQR: 62-249) and, based on self-reporting, participants had been diagnosed as HIV-positive approximately 44 days prior to sample collection (IQR: 23-179). Subtyping revealed that 98.2% were infected with HIV-1 subtype C. Overall, 25 out of 277 patients presented with ≥1 surveillance drug resistance mutation (SDRM, 9.0%, 95% CI: 6.1-13.0%). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most numerous mutations detected (n = 23). Only two patients presented with a protease inhibitor (PI) mutation. In four patients ≥4 SDRMs were detected, which might indicate that these patients were not truly ART-naïve or were infected with a multi-resistant virus.
These results show that the level of antiretroviral drug resistance in ART-naïve South Africans has reached moderate levels, as per the WHO classification. Therefore, regular surveys of pre-treatment drug resistance levels in all regions of South Africa is highly recommended to monitor the changing levels of pre-treatment antiretroviral drug resistance.
为评估HIV-1传播的和/或治疗前抗逆转录病毒药物耐药水平，世界卫生组织（WHO）建议定期开展调查。本研究的目的是评估南非公共部门中开始抗逆转录病毒治疗（ART）的患者中HIV-1抗逆转录病毒药物耐药的频率。
采用规模比例概率抽样进行前瞻性横断面调查。该方法确保根据每个地区接受ART治疗的患者数量按比例收集来自每个省份的样本。样本采集时间为2013年3月至2014年10月。通过逆转录聚合酶链反应（RT-PCR）和桑格测序获得pol序列，并提交至斯坦福校准群体耐药性工具v6.0。
共有277个序列可供分析。大多数参与者为女性（58.8%），中位年龄为34岁（四分位间距：29 - 42岁）。基线CD4细胞计数中位数为149个细胞/mm³（四分位间距：62 - 249），根据自我报告，参与者在样本采集前约44天被诊断为HIV阳性（四分位间距：23 - 179）。亚型分析显示98.2%的患者感染HIV-1 C亚型。总体而言，277例患者中有25例出现≥1种监测药物耐药突变（SDRM，9.0%，95%置信区间：6.1 - 13.0%）。检测到的突变中，非核苷类逆转录酶抑制剂（NNRTI）突变数量最多（n = 23）。仅2例患者出现蛋白酶抑制剂（PI）突变。4例患者检测到≥4种SDRM，这可能表明这些患者并非真正未接受过ART治疗，或者感染了多重耐药病毒。
这些结果表明，按照WHO的分类，南非未接受过ART治疗的人群中抗逆转录病毒药物耐药水平已达到中等程度。因此，强烈建议对南非所有地区治疗前耐药水平进行定期调查，以监测治疗前抗逆转录病毒药物耐药水平的变化。
